Personalized Carbon Monoxide-Loaded Biomimetic Single-Atom Nanozyme for Ferroptosis-Enhanced FLASH & nbsp;Radioimmunotherapy

Lyu, Meng1,2; Luo, Min3; Li, Jingyun4; Akakuru, Ozioma Udochukwu5; Fan, Xiaowan6; Cao, Zhen7; Fan, Kelong6,8,9; Jiang, Wei6

2023-08-31

10.1002/adfm.202306930

ADVANCED FUNCTIONAL MATERIALS   Impact Factor & Quartile

1616-301X

1616-3028

Ultra-high dose rate radiotherapy (FLASH-RT) has emerged as a novel tool for cancer radiotherapy owing to its extremely rapid radiation delivery to target species. Although FLASH-RT can protect normal tissues and organs, tumor self-protection mechanisms limit its therapeutic effect, thus necessitating technological improvement. Here, a multipathway ferroptosis-enhanced radioimmunotherapeutic strategy that combines single-atom nanozyme (SAzyme)-based GSH depletion and CO gas therapy is reported. Personalized FLASH radioimmunotherapy is achieved through encapsulation of the carbon monoxide donor (MnCO)-loaded porous Pd-C SAzyme (SM) within 4T1 cancer cell membranes (CSM). Camouflaging with the cancer cell membrane enables the navigation of the MnCO-loaded Pd-C SAzyme to the tumor region via homologous targeting. There, it releases MnCO, which generates CO from overexpressed H2O2 to induce mitochondrial apoptosis. Furthermore, the generated CO and Pd-C SAzyme oxidized glutathione and downregulates glutathione peroxidase 4 (GPX4) expression to induce ferroptosis. The palladium in the SAzyme of the CSM further enhances the photoelectric effects of FLASH-RT. The CSM-mediated FLASH-RT also invokes potent antitumor immunity, suppressing distant tumors, and immune memory, inhibiting tumor recurrence. This work presents a unique personalized nanozyme and CO gas synergistic approach wherein FLASH radioimmunotherapy avoids damage of normal tissues while simultaneously inducing ferroptosis for orthotopic tumor treatment.

ferroptosis immunotherapy mitochondrial apoptosis single-atom nanozymes ultra-high dose rate radiotherapy

SCI

English

NI Journal Papers

First

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter

WOS:001059351500001

WILEY-V C H VERLAG GMBH

MATERIALS SCIENCE

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp,Affiliated Hosp 1,Dept Gastr, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp,Dept Geriatr,Affiliated Hosp, Shenzhen 518020, Guangdong, Peoples R China
3.Wuhan Univ, Hubei Canc Clin Study Ctr, Dept Radiat & Med Oncol, Hubei Key Lab Tumor Biol Behav,Zhongnan Hosp, Wuhan 430071, Peoples R China
4.Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China
5.Univ Calgary, Schulich Sch Engn, Dept Chem & Petr Engn, Alberta, AB T2N 1N4, Canada
6.Zhengzhou Univ, Acad Med Sci, Nanozyme Med Ctr, Sch Basic Med Sci, Zhengzhou 450001, Peoples R China
7.Maternal & Child Hlth Hosp Hubei Prov, Dept Oncol, Wuhan 430070, Peoples R China
8.Chinese Acad Sci, Inst Biophys, CAS Engn Lab Nanozyme, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China
9.Univ Chinese Acad Sci, Beijing 101408, Peoples R China

Lyu, Meng,Luo, Min,Li, Jingyun,et al. Personalized Carbon Monoxide-Loaded Biomimetic Single-Atom Nanozyme for Ferroptosis-Enhanced FLASH & nbsp;Radioimmunotherapy[J]. ADVANCED FUNCTIONAL MATERIALS,2023.

Lyu, Meng.,Luo, Min.,Li, Jingyun.,Akakuru, Ozioma Udochukwu.,Fan, Xiaowan.,...&Jiang, Wei.(2023).Personalized Carbon Monoxide-Loaded Biomimetic Single-Atom Nanozyme for Ferroptosis-Enhanced FLASH & nbsp;Radioimmunotherapy.ADVANCED FUNCTIONAL MATERIALS.

Lyu, Meng,et al."Personalized Carbon Monoxide-Loaded Biomimetic Single-Atom Nanozyme for Ferroptosis-Enhanced FLASH & nbsp;Radioimmunotherapy".ADVANCED FUNCTIONAL MATERIALS (2023).